CANCELLED! Biological heterogeneity, a phenotypic trait that we harvested to investigate membranes and membrane proteins
Prof. Dimitrios Stamou, University of Copenhagen
Membranes serve multiple crucial roles in cell biology: they act as hosts to membrane proteins, as templates for the nucleation of signalling domains, and as boundaries that define cells and their organelles. We are broadly interested at elucidating molecular mechanisms that regulate the structure, function and organization of membranes and membrane proteins. In this talk I will discuss the role of nanoscopic heterogeneities in regulating biological systems.1-4
The first part of my talk I will focus on a ground-breaking achievement in the investigation of membrane proteins at the single molecule level. We developed a method that can resolve ionic currents with a million-fold higher sensitivity than patch clamp. This allowed us to investigate for the first time the activity/pumping of single transporter molecules. Our measurements revealed that transporters switch on/off like ion channels, a hitherto unrecognised functional heterogeneity that constitutes the mechanistic basis for regulating their macroscopic currents.1
The second part of the talk will be on membranes and discuss the importance of membrane shape in cell biology. The shape of cells and cellular organelles is a remarkably heterogeneous but conserved phenotype, for reasons that remain elusive. Our investigations have revealed the molecular mechanisms that enable distinct membrane shape to affect specifically biological function.2-4
(1) Veshaguri, S.; Christensen, S. M.; Kemmer, G. C.; Ghale, G.; Møller, M. P.; Lohr, C.; Christensen, A. L.; Justesen, B. H.; Jorgensen, I. L.; Schiller, J.; Hatzakis, N. S.; Grabe, M.; Pomorski, T. G.; Stamou, D. Science 2016, 351 (6280), 1469.
(2) Hatzakis, N. S.; Bhatia, V. K.; Larsen, J.; Madsen, K. L.; Bolinger, P.-Y.; Kunding, A. H.; Castillo, J.; Gether, U.; Hedegård, P.; Stamou, D. Nat Chem Biol 2009, 5 (11), 835.
(3) Larsen, J. B.; Jensen, M. B.; Bhatia, V. K.; Pedersen, S. L.; Bjørnholm, T.; Iversen, L.; Uline, M.; Szleifer, I.; Jensen, K. J.; Hatzakis, N. S.; Stamou, D. Nat Chem Biol 2015, 11 (3), 192.
(4) Iversen, L.; Mathiasen, S.; Larsen, J. B.; Stamou, D. Nat Chem Biol 2015, 11 (11), 822.